\u00a0<\/span><\/h3>\nNeeds Grading<\/span>\u00a0<\/span><\/p>\n\n\n\n| \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n\n| \u00a0<\/span><\/td>\n | A ten-year-old boy is brought to clinic by his mother who states that the boy has been listless and not eating. She also notes that he has been easily bruising without trauma as he says he is too tired to go out and play.\u202fHe says his bones hurt sometimes. Mother states the child has had intermittent fevers that respond to acetaminophen.\u202fMaternal history negative for pre, intra, or post-partum problems. Child\u2019s past medical history negative and he easily reached developmental milestones.\u202fPhysical exam reveals a thin, very pale child who has bruises on his arms and legs in no particular pattern. The APRN orders complete blood count (CBC), and complete metabolic profile (CMP). The CBC revealed Hemoglobin of 6.9\/dl, hematocrit of 19%, and platelet count of 80,000\/mm<\/span>3<\/span>.\u202fThe CMP demonstrated a blood urea nitrogen (BUN) of 34m g\/dl and creatinine of 2.9 mg\/dl. The APRN recognizes that the patient appears to have acute leukemia and renal failure and immediately refers the patient to the Emergency Room where a pediatric hematologist has been consulted and is waiting for the boy and his mother. The diagnosis of acute lymphoblastic leukemia\u202f(ALL)\u202fwas made after extensive testing.\u202f\u202f<\/span>\u00a0<\/span><\/p>\n \u00a0<\/span><\/p>\nQuestion 1 of 2:<\/span><\/b>\u00a0<\/span><\/h2>\n\u00a0<\/span><\/p>\nWhat is ALL?\u202f\u202f<\/span><\/i>\u00a0<\/span><\/td>\n \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n\n\n\n\n\n| Selected Answer:\u00a0<\/span>\u00a0<\/span><\/td>\n | ALL is a malignant bone marrow disease where there is a proliferation of early lymphoid precursors that replace the normal bone marrow hematopoietic cells. It is the most common type of leukemia in the US and cancer in children. The malignant cells (lymphoblasts) get arrested in the early development stages, which is caused by abnormal gene expression following abnormalities in the number of chromosomes or\u202f\u202f translocations of chromosomes. When the lymphoblasts proliferate, the number of normal elements in the bone marrow which produce other lines of blood cells decrease.\u202f This explains why most patients usually present with thrombocytopenia, anemia, and neutropenia. In other instances, the lymphoblasts can also infiltrate the beyond the bone marrow, to the lymph nodes, liver, and spleen, causing enlargement.\u00a0<\/span>\u00a0<\/span><\/td>\n<\/tr>\n\n| Correct Answer:\u00a0<\/span>\u00a0<\/span><\/td>\n | \u00a0<\/span><\/p>\n Acute lymphoblastic leukemia (ALL) is a malignant (clonal) disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. ALL is the most common type of cancer and leukemia in children in the United States.<\/span>\u00a0<\/span><\/p>\nThe malignant cells of acute lymphoblastic leukemia (ALL) are lymphoid precursor cells (ie, lymphoblasts) that are arrested in an early stage of development. This arrest is caused by an abnormal expression of genes, often as a result of chromosomal translocations or abnormalities of chromosome number.<\/span>\u00a0<\/span><\/p>\nThese aberrant lymphoblasts proliferate, reducing the number of the normal marrow elements that produce other blood cell lines (red blood cells, platelets, and neutrophils). Consequently, anemia, thrombocytopenia, and neutropenia occur, although typically to a lesser degree than is seen in acute myeloid leukemia.\u202fLymphoblasts can also infiltrate outside the marrow, particularly in the liver, spleen, and lymph nodes, resulting in enlargement of the latter organs.<\/span>\u00a0<\/span><\/td>\n<\/tr>\n\n| Response Feedback:\u00a0<\/span>\u00a0<\/span><\/td>\n | [None Given]\u00a0<\/span>\u00a0<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\nQuestion 2\u00a0<\/span><\/b>\u00a0<\/span><\/h2>\nNeeds Grading<\/span>\u00a0<\/span><\/p>\n\n\n\n| \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n\n| \u00a0<\/span><\/td>\n | A ten-year-old boy is brought to clinic by his mother who states that the boy has been listless and not eating. She also notes that he has been easily bruising without trauma as he says he is too tired to go out and play.\u202fHe says his bones hurt sometimes. Mother states the child has had intermittent fevers that respond to acetaminophen.\u202fMaternal history negative for pre, intra, or post-partum problems. Child\u2019s past medical history negative and he easily reached developmental milestones.\u202fPhysical exam reveals a thin, very pale child who has bruises on his arms and legs in no particular pattern. The APRN orders complete blood count (CBC), and complete metabolic profile (CMP). The CBC revealed Hemoglobin of 6.9\/dl, hematocrit of 19%, and platelet count of 80,000\/mm<\/span>3<\/span>.\u202fThe CMP demonstrated a blood urea nitrogen (BUN) of 34m g\/dl and creatinine of 2.9 mg\/dl. The APRN recognizes that the patient appears to have acute leukemia and renal failure and immediately refers the patient to the Emergency Room where a pediatric hematologist has been consulted and is waiting for the boy and his mother. The diagnosis of acute lymphoblastic leukemia\u202f(ALL)\u202fwas made after extensive testing.\u202f\u202f<\/span>\u00a0<\/span><\/p>\nQuestion 2 of 2:<\/span><\/b>\u00a0<\/span><\/h2>\n\u00a0<\/span><\/p>\nHow does renal failure occur in some patients with ALL?\u202f<\/span><\/i>\u00a0<\/span><\/p>\n\u00a0<\/span><\/td>\n \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n\n\n\n\n\n| Selected Answer:\u00a0<\/span>\u00a0<\/span><\/td>\n | In patients with ALL, renal failure occurs as a result of hyperuricemia and this can be at the point of diagnosis or active treatment. Cellular destruction during the metabolism of purine influences an increase in the levels of uric. Since major paths of excretion are through the kidneys, the urates can end up precipitating in the ureters or renal tubules resulting in symptoms of oliguria and subsequent acute renal failure.\u00a0<\/span>\u00a0<\/span><\/p>\n \u00a0<\/span><\/td>\n<\/tr>\n\n| Correct Answer:\u00a0<\/span>\u00a0<\/span><\/td>\n | \u00a0<\/span><\/p>\n Renal failure as a result of hyperuricemia can be associated with ALL, particularly at diagnosis or during active treatment. Uric levels rise as an end product of purine metabolism from cellular destruction. Because the major excretory pathway is through the kidneys, urates can precipitate in renal tubules or ureters and can lead to oliguria and acute renal failure.<\/span>\u00a0<\/span><\/td>\n<\/tr>\n\n| Response Feedback:\u00a0<\/span>\u00a0<\/span><\/td>\n | [None Given]\u00a0<\/span>\u00a0<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\nQuestion 3\u00a0<\/span><\/b>\u00a0<\/span><\/h2>\n\n\n\n| \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n\n| \u00a0<\/span><\/td>\n | A\u202f12-year-old\u202ffemale with known sickle cell disease (SCD)\u202fpresent to the Emergency Room\u202fin sickle cell crisis.\u202fThe patient is crying with pain and states\u202fthis is the third acute episode\u202fshe has had in the last nine months. Both parents are present and appear very anxious and teary eyed.\u202fA diagnosis of acute sickle cell crisis was made.\u202fAppropriate therapeutic interventions were initiated\u202fby the\u202fAPRN\u202fand the patient\u2019s pain level\u202fdecreased,\u202fand she was transferred to the pediatric intensive\u202fcare\u202funit\u202f(PICU)\u202ffor observation and further management.\u202f\u202f<\/span>\u00a0<\/span><\/p>\n \u00a0<\/span><\/p>\nQuestion 1 of 2:<\/span><\/b>\u00a0<\/span><\/h2>\n\u00a0<\/span><\/p>\nWhat is the pathophysiology of acute SCD crisis and why is pain the predominate\u202ffeature of acute crises?\u202f\u202f<\/span><\/i>\u00a0<\/span><\/p>\n\u00a0<\/span><\/td>\n \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n\n\n\n\n\n| Selected Answer:\u00a0<\/span>\u00a0<\/span><\/td>\n | Vaso-occlusive crises occur in more than half of individuals who have homozygous HbS although frequency tends to vary. Potential triggers of crises may include; dehydration, hypoxemia, and potential changes in body temperature. Most people with HbSS have a chronic low level of pain in joint and bones. \u202fRBCs with a sickle shape are stickier and have high amounts of adhesion molecules. During an inflammatory reaction, leukocytes release mediators which increase the adhesion of molecules to endothelial cells. These processes influence sickled erythrocytes to be arrested as they move into the microvascular compartment. The RBCs become stagnant and sluggish in inflamed vascular vessels increasing their likelihood to sickle, low oxygen tension, and obstruction. The lysed RBCs produce hemoglobin and the free hemoglobin can bind and inactivate nitric oxide, a vasodilator that also inhibits the aggregation of platelets. These processes influence a decrease in the Ph of blood which decreases the affinity of hemoglobin for oxygen increasing the amount of HbS that is deoxygenated in the tension of oxygen, and a predisposition to sickling. As the lungs receive less oxygen, there is a drop in PO2 which further influences sickling. The pain experienced\u202f\u202f is caused by the lack of oxygen in major bones and organs and can result in \u202fthe death of vital organs\u202f and ischemia.\u00a0<\/span>\u00a0<\/span><\/p>\n \u00a0<\/span><\/td>\n<\/tr>\n\n| Correct Answer:\u00a0<\/span>\u00a0<\/span><\/td>\n | \u00a0<\/span><\/p>\n Approximately half the individuals with homozygous HbS disease experience vaso-occlusive crises. The frequency of crises is extremely variable. Some individuals have as many as 6 or more episodes annually, whereas others may have episodes only at great intervals or none at all. Each individual typically has a consistent pattern for crisis frequency. Triggers of vaso-occlusive crisis include the following:<\/span>\u00a0<\/span><\/p>\n\n- Hypoxemia: May be due to acute chest syndrome or respiratory complications<\/span>\u00a0<\/span><\/li>\n
- Dehydration: Acidosis results in a shift of the oxygen dissociation curve<\/span>\u00a0<\/span><\/li>\n
- Changes in body temperature (eg, an increase due to fever or a decrease due to environmental temperature change)<\/span>\u00a0<\/span><\/li>\n<\/ul>\n
Many individuals with HbSS experience chronic low-level pain, mainly in bones and joints. Intermittent vaso-occlusive crises may be superimposed, or chronic low-level pain may be the only expression of the disease.<\/span>\u00a0<\/span><\/p>\nSickle RBCs express higher than normal amounts of adhesion molecules and are sticky. During inflammatory reactions, leukocyte release of mediators increases the expression of adhesion molecules on endothelial cells. These reactions further promote sickled erythrocytes to be come arrested during movement through the microvascular. The sluggish and stagnant red cells within the inflamed vascular vessels result in extended exposure to low oxygen tension, sickling, and vascular obstruction. Lysed sickle erythrocytes release hemoglobin and free hemoglobin can bind and inactivate nitic oxide (NO), which is a powerful vasodilator and inhibitor of platelet aggregation. Decreased blood pH reduces hemoglobin affinity for oxygen leading to an increasing fraction of deoxygenated HbS at any oxygen tension and predisposition to sickling. As less oxygen is taken up by hemoglobin in the lungs, the PO2 drops promoting additional sickling.<\/span>\u00a0<\/span><\/p>\nThe intense pain of an acute crisis is due to lack of oxygen to major organs and bones. The lack of oxygen leads to ischemia and organ death.<\/span>\u00a0<\/span><\/td>\n<\/tr>\n\n| Response Feedback:\u00a0<\/span>\u00a0<\/span><\/td>\n | [None Given]\u00a0<\/span>\u00a0<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\nQuestion 4\u00a0<\/span><\/b><\/h2>\n\u00a0<\/span><\/p>\nNeeds Grading<\/span>\u00a0<\/span><\/p>\n\n\n\n| \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n\n| \u00a0<\/span><\/td>\n | A\u202f12-year-old\u202ffemale with known sickle cell disease (SCD)\u202fpresent to the Emergency Room\u202fin sickle cell crisis.\u202fThe patient is crying with pain and states\u202fthis is the third acute episode\u202fshe has had in the last nine months. Both parents are present and appear very anxious and teary eyed.\u202fA diagnosis of acute sickle cell crisis was made.\u202fAppropriate therapeutic interventions were initiated\u202fby the\u202fAPRN\u202fand the patient\u2019s pain level\u202fdecreased,\u202fand she was transferred to the pediatric intensive\u202fcare\u202funit\u202f(PICU)\u202ffor observation and further management.\u202f\u202f<\/span>\u00a0<\/span><\/p>\nQuestion 2 of 2:<\/span><\/b>\u00a0<\/span><\/h3>\n\u00a0<\/span><\/p>\nDiscuss the genetic\u202fbasis for SCD.<\/span><\/i>\u00a0<\/span><\/p>\n\u00a0<\/span><\/td>\n \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n | \u00a0<\/span><\/td>\n<\/tr>\n\n\n\n\n\n| Selected Answer:\u00a0<\/span>\u00a0<\/span><\/td>\n | SCD comprises of all genotypes that contain at least one sickle gene where the HbS comprises half of the present hemoglobin such as HbSS (sickle cell anemia), HbS\/b+ thalassemia, HbS\/ b-0 thalassemia, and HbSC disease. The heterozygous form (carriers) have up to 40% of HbS, no anemia, hematuria, and isosthenuria. SCD causes an illness but the trait does not. However, individuals who inherit two sickle hemoglobin genes from both parents can have SCD\u00a0<\/span>\u00a0<\/span><\/p>\n \u00a0<\/span><\/td>\n<\/tr>\n\n| Correct Answer:\u00a0<\/span>\u00a0<\/span><\/td>\n | \u00a0<\/span><\/p>\n SCD denotes all genotypes containing at least one sickle gene, in which HbS makes up at least half the hemoglobin present. Major sickle genotypes described so far include the following:<\/span>\u00a0<\/span><\/p>\n\n- HbSS disease or sickle cell anemia (the most common form) – Homozygote for the S globin with usually a severe or moderately severe phenotype and with the shortest survival<\/span>\u00a0<\/span><\/li>\n
- HbS\/b-0 thalassemia – Double heterozygote for HbS and b-0 thalassemia; clinically indistinguishable from sickle cell anemia (SCA)<\/span>\u00a0<\/span><\/li>\n
- HbS\/b+ thalassemia – Mild-to-moderate severity with variability in different ethnicities<\/span>\u00a0<\/span><\/li>\n
- HbSC disease – Double heterozygote for HbS and HbC characterized by moderate clinical severity<\/span>\u00a0<\/span><\/li>\n
- HbS\/hereditary persistence of fetal Hb (S\/HPHP) – Very mild or asymptomatic phenotype<\/span>\u00a0<\/span><\/li>\n<\/ul>\n
Sickle cell trait or the carrier state is the heterozygous form characterized by the presence of around 40% HbS, absence of anemia, inability to concentrate urine (isosthenuria), and hematuria. Under conditions leading to hypoxia, it may become a\u202f pathologic risk factor. Sickle cell disease produces illness, while sickle cell trait usually does not. People who inherit two genes for sickle hemoglobin (one from each parent) have sickle cell disease. With a few exceptions, a child can inherit sickle cell disease only if both parents have one gene for sickle cell hemoglobin<\/span>\u00a0<\/span><\/td>\n<\/tr>\n\n | | | | | | | | | | | | | | | | | | | | | | | | | | | |